1. Chromatin-associated YTHDC1 coordinates heat-induced reprogramming of gene expression.
- Author
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Timcheva, Kalina, Dufour, Solenne, Touat-Todeschini, Leila, Burnard, Callum, Carpentier, Marie-Christine, Chuffart, Florent, Merret, Rémy, Helsmoortel, Marion, Ferré, Sabrina, Grézy, Aude, Couté, Yohann, Rousseaux, Sophie, Khochbin, Saadi, Vourc'h, Claire, Bousquet-Antonelli, Cécile, Kiernan, Rosemary, Seigneurin-Berny, Daphné, and Verdel, André
- Abstract
Heat stress (HS) induces a cellular response leading to profound changes in gene expression. Here, we show that human YTHDC1, a reader of N
6 -methyladenosine (m6 A) RNA modification, mostly associates to the chromatin fraction and that HS induces a redistribution of YTHDC1 across the genome, including to heat-induced heat shock protein (HSP) genes. YTHDC1 binding to m6 A-modified HSP transcripts co-transcriptionally promotes expression of HSPs. In parallel, hundreds of the genes enriched in YTHDC1 during HS have their transcripts undergoing YTHDC1- and m6 A-dependent intron retention. Later, YTHDC1 concentrates within nuclear stress bodies (nSBs) where it binds to m6 A-modified SATIII non-coding RNAs, produced in an HSF1-dependent manner upon HS. These findings reveal that YTHDC1 plays a central role in a chromatin-associated m6 A-based reprogramming of gene expression during HS. Furthermore, they support the model where the subsequent and temporary sequestration of YTHDC1 within nSBs calibrates the timing of this YTHDC1-dependent gene expression reprogramming. [Display omitted] • YTHDC1 predominantly localizes to chromatin, and heat stress reshapes its genomic location • Upon heat stress, YTHDC1 binds to m6 A-modified HSP RNAs and promotes expression of HSPs • Upon heat stress, YTHDC1 also mediates a broad m6 A-dependent intron retention regulation • Later, YTHDC1 relocates to nuclear stress bodies by binding to m6 A-modified SATIII ncRNAs Timcheva et al. show that human m6 A reader YTHDC1 is a key player in heat-induced gene expression reprogramming. Upon heat stress, YTHDC1 co-transcriptionally promotes expression of HSPs and regulates intron retention of hundreds of transcripts. Later, as these two YTHDC1-dependent activities diminish, YTHDC1 relocates to nuclear stress bodies. [ABSTRACT FROM AUTHOR]- Published
- 2022
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